for joining us this afternoon. I'm Vijay Kumar, the Life Science Device Analyst here at Evercore. A pleasure to have with us Novocure. We have Chairman Bill Doyle with us, and Adam Daney from Investor Relations. Bill, I know you guys had some exciting news with the pancreatic cancer, so congratulations. Before we dive into the Q&A, maybe some opening remarks from you on who Novocure is and what this trial was about.
Sure. So good afternoon, Vijay. Thank you very much for inviting us. And thanks to everybody in the room and everybody else who's listening remotely. Vijay knows us well. Novocure was founded 24 years ago now to develop and commercialize what was, at the time, a very unexpected modality using electric fields to target the electrical properties of cancer cells to fight solid tumors. We started with three people in a basement in Haifa, Israel. And from there, took our therapy into animals, of course, and then into humans. And our first focus was on the deadly brain cancer, glioblastoma. And to make a 24-year story just a few minutes, we were successful in a phase three trial treating newly diagnosed GBM. It's one of the only trials to show a significant improvement in this very challenging disease. We launched in newly diagnosed GBM early in 2016.
Over the last eight years, have brought the therapy to virtually every center in the U.S., Germany, France, Sweden, Austria, Switzerland, in Europe. From there, we knew that our physics could work in any solid tumor where we could deliver an electric field of an appropriate intensity. We took the profits that we made from our GBM business, and we invested those profits in a development program to bring the therapy to other cancer indications. I'm delighted, in fact. 2024 was a year of hard work, but a year of accomplishment from Novocure. We completed the year with two new PMAs, one in non-small cell lung cancer and one for the next generation of our equipment, which I've brought with me, and also two successful phase 3 trials, one in brain mets from non-small cell lung cancer.
And as we announced on Monday, a second in first-line pancreatic cancer. So I think we're positioned to now go from a successful company treating patients with glioblastoma. And by the way, in a market where we still think we have more opportunity to serve more patients and to grow, but really on the threshold of bringing the therapy to much larger groups of patients in these extremely difficult to treat cancers. So that's the quick intro to Novocure.
Now, thanks for that background, Bill. Maybe we'll start with that panel where that's the most topical, and it's a very hard, difficult to treat cancer. For those not familiar, explain to us what this trial was about. What kind of patients did you look at, and are these results clinically meaningful?
Yeah. So I don't think I have to tell anybody that pancreatic cancer is one of the most difficult and challenging diagnoses, perhaps in medicine, and it's also been an area that has been incredibly stubborn and difficult, described by many as a wasteland. The immunotherapies have not worked in this area. Targeted therapies have not really worked. As I said, our therapy depends on physics as opposed to specific biology, and we know that when we can get our fields to the region of the cancer, that we can have an effect, so we designed this phase three trial to treat the subset of patients, as I mentioned already, in the first-line who are non-resectable, and maybe I should take a step back. When patients are diagnosed with pancreatic cancer, they usually fall into one of three buckets.
Pancreatic cancer, because it's very often either not symptomatic or the symptoms can be confused with other GI diseases, it's almost always diagnosed late. So patients are either diagnosed at a point where they are said to have metastatic disease, one category, locally advanced non-resectable disease, or early resectable. That fraction that is early and resectable is a very small percentage. Numbers are quoted around 5% or 10%. The majority are in that later group, about 60%. We focused on the 30% that are locally advanced. So this was a trial in that 30% of diagnoses. These patients today receive chemotherapy, usually one of two regimens, FOLFIRINOX or gemcitabine Abraxane, GemAbraxane. They're split about 50/50. And we chose to add Tumor Treating Fields to GemAbraxane in the locally advanced population compared to head-to-head, randomized one-to-one GemAbraxane alone.
No trial, phase 3 trial, has ever been successful in this population, just to put this in perspective, and we showed a statistically and what we announced, and again, we're always in this situation where we try and give a top-line data to give you an appreciation, but we're holding the bulk of the data for a scientific presentation that will happen next year, but what we've announced is a statistically significant and clinically meaningful increase in the overall survival in the intent to treat population, so this is great news for patients. It's, quite frankly, great news for Novocure, but it validates the physics that I described, and I just couldn't be happier, to be honest.
Yeah, absolutely. It's nice to see a trial actually succeed in pancreatic. On that two-month, Bill, I think some questions we've been getting is, what is the real-world applicability? Yes, you did hit that significance, but you need to wear the device for 18 hours. So maybe talk about the real-world applicability and clinical relevance of what the two months mean.
Yeah. So as is always the case, what I think doesn't matter, what KOLs think and what practitioners think is what matters. And I have to say the early feedback we have has been extraordinary in this regard. So doctors have these patients in their offices. They have nothing to offer them, but these old chemotherapy regimens. They have expressed tremendous enthusiasm for the benefit. I think they understand, or at least as they learn more, that in every cancer that we've studied, there are a dose-response. And so we'll have the opportunity to educate these patients as well that more use is better. We tried to give a couple of other hints without jeopardizing our possibility. We spoke to the 33% increase in life expectancy at two years in these data. So what we're hearing is that this is clinically meaningful and will be used.
We hear things like practice changing, game changing. I think it's, in many ways, just a reflection of how difficult this disease has been to make any progress at all.
Fantastic. And on the full data, Bill, is there a pancreatic cancer or is this ASCO? When do you think we might see the full results?
So we want to get it to the world as soon as possible. We don't know yet. I mean, we gave the top line Monday. It's Wednesday. So I need more than a couple of days. But what we aspire to is a podium at one of the most important cancer meetings. We also aspire to a publication in a top. The perfect scenario would be a peer-reviewed publication that would be concurrent with the presentation. And that's what we're working toward.
Understood, and since you brought up the 33% increase in life expectancy at two years, Bill, I know it's relative to control arm, but how should we interpret that increase at two years? Is that a drop-off in the control arm? Is that what's driving this? Is that a dose response because these patients were in a more regular on therapy?
Yeah. So Vijay, I'd love to talk more about the data, but I can't. So I can only refer. We tried to give two data points that would allow people to infer some things about the Kaplan-Meier curves. And I think you can infer positively based on that. What I will say is this was a trial of very straightforward design, randomized one-to-one, standard of care chemotherapy compared to standard of care plus Tumor Treating Fields therapy. So there was nothing unusual about the trial design. And I think the data should be very interpretable when presented at a conference.
Understood. Maybe one more on this clinical endpoint. Is quality of life? Was it measured in the trial? Will that be published?
Yeah. We always measure quality of life. And quite frankly, it's one of the great advantages of our therapy, right, that we're able to deliver our added benefit without where we see no systemic toxicity. And the only device-related adverse event that we see is skin irritation, which is in virtually all cases manageable. And it's one of the things that we're doing product development to continue to improve with new materials, both to improve the ease of use, the tolerability, and also to increase the dose, right? Because one way you can increase the dose of Tumor Treating Fields is to wear it more. Another way is for us to deliver more energy. And that's a materials opportunity and something that we're working on. And the first real improvement is in these GBM arrays. As I said, I was delighted.
It was maybe a little more muted than success in pancreatic cancer, but we did receive the PMA approval for these arrays just a couple of weeks ago, and we've started rolling them out in the U.S., so I think this is a tailwind to the GBM business as well.
Absolutely. And we'll certainly get into that. But sticking on to pancreatic, Bill, does PFS matter? What matters to clinicians? Is it overall survival?
Yeah, it's overall survival. The gold standard here is overall survival in the intent-to-treat group. And that's how the trial was designed. And that's why I say it's a very straightforward, easily interpretable trial and easily interpretable result.
From an FDA submission timing, is that six months in the middle of next year?
Yeah, so I'll give everyone here the generic answer to that question, which is six months to pull the file together and get it submitted, and then 12 months for review. We were very pleased with the metastatic data that we received Breakthrough Device Designation. That helps in terms of putting the file on the top of the pile at the FDA. We'll clearly look to that in this application as well, so what I say to the outside is 18 months. What I say to the inside is you better beat that, and we'll see where we wind up.
Understood, and given there are two different chemo regimens in the patient population, right, is there a view on what the label should look like? Would that be very specific to patients on GemAbraxane, or would it be broader?
Yeah, and this is an easier question to answer for this trial. We had a harder time answering it for LUNAR until we actually showed the label, but we would expect the label to be consistent with the primary endpoint, so in this case, it's TTF plus GemAbraxane.
Gotcha. And how should we think about the U.S. TAM, Bill, given it's applicable to the GemAbraxane population?
Yeah. So maybe to expand on that, I said earlier that patients today are given one of two chemo regimens, FOLFIRINOX or GemAbraxane. There's never been a head-to-head trial of the two. And there is some, and comparing one trial to another has all sorts of challenges, particularly when the differences are small, right? But there is some feeling in the community that FOLFIRINOX may offer some advantages. However, it is a highly toxic regimen. And so it's typically given to the younger, healthiest patients, many of whom will drop off it and then go back to GemAbraxane. So we'll have to see how this plays out. But I think the possibility of giving GemAbraxane plus TTF and getting a higher expectation for overall survival and avoiding some of the FOLFIRINOX tox offers a real opportunity. And then I would expect there'll be ISTs.
This will clearly be studied now with FOLFIRINOX, and we'll be able to report those data in time.
Understood. So would about 10,000 patients in the U.S. be reasonable?
The number we're using is 15, actually.
15.
Yeah. So it's definitely bigger than the GBM opportunity. But on label, first indication, our U.S. number that we're suggesting is 15,000.
Would that be 15,000 patients who are on GemAbraxane, Bill, or is that the overall?
That's the non-resectable locally advanced number that we think will be eligible for this therapy.
Okay. Understood. What's the OUS opportunity for this? How should we think of Europe and China?
I haven't done the breakdown, but we will launch. First of all, we will file in the US, Europe, and Japan immediately. Those are our three most important markets. They will be followed by the appropriate local filings in the core markets in Europe. It's been too early, so we haven't done the full launch plan yet. If I go back to LUNAR, which we can talk about, where our launch plan centers around the US and Germany at risk. What I mean by at risk, I mean at risk of reimbursement, where we can apply on a name patient basis as we work to global reimbursement. I am highly confident we'll do exactly the same thing with pancreatic cancer. We'll work in Japan to get reimbursement as quickly as we can in parallel with the approval.
But really too early to talk about details of the plan. Our goal is to get the FDA approval, call it mid-2026, and be ready to launch just like we were ready to launch with Lung when we get the piece of paper.
Understood. And maybe last two questions here on pancreatic, Bill. The two other dynamics which go into the peak revenue sort of math is one is duration of therapy. We've generally used, I think, eight months for GBM. Would that be an applicable number here in pancreatic?
The number that we've guided to in Lung is six months. And I think I would anchor to that number to start is six. When we started GBM, the number was lower, of course. And we worked our way up through patient education. We would expect to do that here too. But I would anchor to six months for sort of the launch years.
Six, that's for lung, pancreatic?
And pancreatic.
And pancreatic.
Yeah.
Fantastic. And then the other math is the penetration rate, I think. For some cancers, we've used 10%. Some cancers, we've used 30%. But given this is a difficult cancer, we haven't had any approvals in a long time. Should that penetration number be higher for pancreatic?
So here we're guessing, right? Based on and we're in GBM. We're around 40. And we're working to raise that. I think this is, however, apples and oranges with GBM. My hope is it would be much higher than that, Vijay. But that's not one where I can tell you that the early enthusiasm suggests that. But I can't predict it with any precision.
Understood. And then maybe switching gears now to LUNAR. The label, I think, surprised a lot of people, right? It was a pretty broad, clean label out there. I guess now that we've had the FDA approval, you've had some time to sort of start your initial commercial activities. What's been the feedback in the field, and how should we think of the lung opportunity?
Yeah. So this has been the biggest disconnect between what I would say is reality on the ground and perception of the market. And what do I mean by that? I know the bear case. The bear case is we delivered a phase three data set with LUNAR. The primary endpoint was met, which was treating tumor treating fields. First of all, patient population. Second, third line, non-small cell lung cancer after platinum failure. And we treated those patients, half of whom approximately received chemotherapy in that line, half of whom received immunotherapy. The primary endpoint was the combination where we showed statistically significant improvement in overall survival. I said from day one, that's what we're submitting to the FDA. It's the primary endpoint. That's the label I expect. I clearly heard every other opinion in the book, but that's the label we received, okay?
So now the question becomes practice. And the second part of the, I would say, the bear case was that the data were profound when you combined with IO, but IO is not used in the second line anymore. So congratulations, but you have no patients. And what we said we're hearing is that these are patients who, first of all, the doctors have, right? They've failed platinum. They're in the office. Immunotherapy has moved to the first line. So they have nothing to offer these patients except docetaxel, which as a single agent is doing very little. What we were hearing from clinicians at the time was that many of these patients were being given IO in the second line. And these would be the perfect patients for our therapy.
ASCO a year ago, June, the round numbers for these patients, about 10%, were being rechallenged, having nothing to do with Novocure. And you may know the numbers better than I, but that number has gone up to like 40%, 50%. So the patients come off platinum, but either stay on the IO or are rechallenged with a different IO. We're getting tremendous enthusiasm to add Tumor Treating Fields to that cohort. And my guess, and it's a guess, but that cohort's going to keep growing. And for those patients who, for whatever reason, can't get rechallenged and are going to be on docetaxel, some of those will also get Tumor Treating Fields, the ones that really want to keep going, really want to try, really want to comply.
But my net on all this is I think I don't know if there's zero in the stock or negative in the stock for this market. But I think this opportunity is bigger than GBM and bigger than pancreatic cancer with the label as it stands. And from here, of course, the goal is to bring it to the front line. Now we're going to have to do that trial, and that's going to take some years. But not do I think it's zero. I think it's the biggest opportunity that we have before us. Another thing that was helpful here, of course, was the great result in METIS, which was it's the same cancer in the brain where we showed this 12-month prolongation in progression and 12-month prolongation in neurocognitive decline.
That is also very supportive, I think, to the story of Tumor Treating Fields in non-small cell lung cancer.
Now, I certainly think the comment about lung being a bigger option with existing label. I think there is a disconnect with the market, Bill, for sure. It's one where the market has struggled with how to size that opportunity. But I'm curious. Your comments seem pretty bullish, right? What are you hearing from the field when your sales force has started reaching out to some of these medical oncologists?
Oh, absolutely. So one of the things that played out in 2024, and I have to say, I'm extremely pleased with the way the organization came together and performed in 2024. We started the year with three very specific goals. We wanted to grow GBM. GBM had plateaued for a number of years and plateaued at a point where it shouldn't have plateaued, where many more patients could continue to benefit, and so we reorganized our whole field-facing organization and gave them the mission to grow, which they have, okay? The second objective was to deliver on the pipeline, and that was specifically METIS and PANOVA, which we have, as of Monday, delivered, but the third was to launch LUNAR, and it ended up bureaucracy, our FDA approval. We got the approval we wanted. It came a little bit late, so we had time.
Our sales force was fully up, running in the field, at the shows, at the conferences, running ad boards, doing medical education. And I think that preparation has really paid off for us. If you do a KOL call and you call someone who's never even heard of Tumor Treating Fields, you're going to get, well, I'm not sure. It has to be proven. If you get a clinician after they've gone through one of our ad boards and they've been reminded of all the data, they're going to say, I have patients. And that's what we're seeing. So we're receiving scripts. We have patients on therapy. We've said that our focus in the first part of the launch is not on numbers. It's on getting the right patients. And what do I mean by that?
The right patients for Tumor Treating Fields are patients who have just failed platinum, okay, and are in the second or third line. Doctors do have patients who are, quite frankly, ready to go to hospice, and the families may be saying, what can we do? What can we do? We don't want those patients in the first part of the launch because they're not going to be able to comply. The doctor experience may not be positive. We want those patients who can really benefit, and we want those early prescriber experiences to be very positive, and that's what's happening as we launch in the U.S.
And how do you think about the ramp here in terms of patient adoption, adoption by KOLs, clinicians? Obviously, it's a pretty big pool in a CLC.
Yeah. So as I said, right now, I'm focused on the maximum number of positive experiences rather than the maximum number of patients. This is another fact for a technology like this. Doctors are going to prescribe it for a couple of patients and see how they do, make sure that there's not something in the logistics that make it difficult for their practice. I'll remind everyone, we've taken those logistics on ourselves. So we receive a script. We send a tech to the patient's house. We teach them how to use the equipment. We provide the service and follow-up. So the docs don't have to inventory. They don't have to bill. We do all the billing. But a doctor practice doesn't know that on day one.
So there's a little bit of mystery just surrounding the practice dynamics that we are in the process of making sure it's very clear just how easy this is to prescribe.
When you think about the building that support infrastructure to ensure patients have the right experience, how large is that infrastructure of salespeople and support personnel, if you will, to support Lung launch?
So the good news is we know how to do this, right, because we've learned from all the mistakes and false starts because we created this market, right, with GBM. So the number of field-facing people is about 50 to start. I think that number, and that includes both salespeople and medical educators. And we have both, as you would expect. The variable number is the third group, which is what we call the device support specialists, which we add those with volume. And these are people that we know how to onboard. We know how to train. They're not medical professionals. They're people with empathy who can provide the patient support and follow-up, very scalable in our organization.
Just remind us on reimbursement pathway here. When do you expect to receive reimbursement, or at least what percentage of population do you expect coverage for TTF over the next two years?
Yeah. So let me divide it one year and two years. So I think the Wall Street consensus for 2025 is 10-15. We think that's a reasonable number to have in the models. The way this works is that we take a patient. We confirm that they're on label, and this is important for us. And then in the U.S. and Germany, we will treat that patient. We call it at risk, but what that really means is that we'll start treating the patient, and then we will apply to the patient's payer for payment. And at least in GBM, we get paid for those patients. But sometimes there's a cycle, right? It's so-called name patient basis. We have to go to the chief medical officer of the plan. And for an FDA-approved product in an indication like this, we get those.
You collect enough of those patients that have been approved for a plan on a per-patient basis, then you can say, guys, let's stop this. Let's get this on the plan. And we go plan by plan by plan. And this is, again, work we know how to do. The second, that's for the commercial payers. For Medicare and for GBM, the round number is 60-40, 60 commercial, 40 Medicare. Lung cancer's flipped. It's a larger proportion is Medicare, smaller proportion is commercial. We then have to go, and when we have enough Medicare patients that we've treated and we've built, we have to go to Medicare and say, okay, it's time to add. I wish that there were a defined process with Medicare with a defined timeline. There's not. And in fact, we're working hard on the legislative front to maybe institute that.
We have a lot of bipartisan support, in fact, to do that. This is where, because we have already broken a lot of that ground with GBM, you can imagine when we went in with GBM the first time, it's, what is this voodoo? Now they have approved it, are paying for it for GBM. We're going in again with phase three data. I'm at least hopeful that this process will be a little more straightforward than it was when we did the same thing for the first time.
Maybe the last two questions on the lung topic here, Bill, because you went through this process in GBM. Do you know what percentage of patients are paid when you go back to the payers and submit a claim? When we don't have a reimbursement code, is it half, 20%? And follow-up is, last time we had a MedCAC panel meeting, do we need one for lung?
So I'm going to answer that question. In GBM, on label, we were ultimately paid for all of the patients. The ones that we weren't paid for are the ones that were off label. So that's what happened in retrospect was a careful examination of which patients were on label and which patients were off label. And the payers use that as their criterion. And so we're being very careful. Lung is bigger than GBM, right? So we're at more the dollar number that will be out of pocket until we're paid is going to be larger. So we're being very careful about only treating patients who are on label. And my expectation would be to get paid for essentially all of them in time. Your second question had to do with.
The panel, MedCAC.
So there's two panels that we had with GBM. So FDA and CMS. So we're focused on payment. So CMS, they did convene a panel to ask the question of the community, should we pay for this in GBM? And it was a bit nerve-wracking. But that panel came back and said, yes, we should pay for it. Quite frankly, I don't know exactly what to expect here. We're not afraid of these panels. Again, in lung cancer here where there's no other good options, if they want a panel, would be happy with a panel. But I don't have any visibility as to whether CMS will ask for a panel. I also get asked, do you think the FDA will want a panel for PANOVA? Just looping back, I would guess no, but still a guess.
I would have thought between lung and pancreatic, it was lung. If lung got through, then yeah, pancreatic should be clean. As we look at the next two, three years, Bill, what other major catalysts should we be looking forward to?
So as I said, when I spoke at J.P. Morgan last January, I got asked afterwards, gee, how come you didn't act with more enthusiasm? And I said, 2024 is a year of execution here. I don't want to talk about what we're going to do. I need to show that I can grow GBM, that I can deliver the pipeline, and that I can launch lung. So I think in 2025, those themes will continue. We need to continue to grow GBM, number one. On the launch side, we need to get METIS filed and approved. And we need to get PANOVA filed, accepted, and approved. Whether both of those will be approved next year, but they'll definitely get filed. And we need to get on the podium with PANOVA. And we need to get that published in a top peer-reviewed journal.
We need to deliver some metrics on lung so that people see the benefit of the lung, and then we will anticipate PANOVA-4 and TRIDENT early in 2026. Those will be the next big data sets that will come early in 2026, so another year of execution. Maybe in the last couple of minutes, the other thing I'll mention that we did this year is my partner, Asaf Danziger; he and I have been working together for 22 years. I think we've also now set Novocure up very consciously with the next generation of management to take the opportunity from an idea through GBM, but now to continue to build into a multi-specialty company, so Ashley Cordova will take over as CEO. Frank Leonard has taken over as the president of overall commercial, really streamlined that.
We've brought in a new CMO, a new head of HR, and most recently, a new CFO from Moderna. So we have a really energetic, experienced, right mix, I think, between insiders and outsiders, top-tier management to execute.
Gotcha. And just because you brought up PANOVA-4, that's in metastatic.
Correct.
Unresectable pancreatic cancer.
Yes.
Given that survival in a median overall survival, it's much shorter. I think it's under a year, and you finished enrollment pretty recently. Shouldn't we be expecting headline results late next year around this time on PANOVA-4?
I would hope it be sooner than that.
Sooner than that. Okay.
Yeah.
And then I guess in the last two minutes here, Bill, what is the stock? When I look at that, take a step back, right? This is one where in some ways, we've round tripped. We've seen the peaks. We've seen the lows. What should be the next five years for Novocure? Should this be like a 15%-20% consistent top-line growth company because of pipeline? The platform teases us back. And two, is that growth going to be profitable growth, or does Novocure need to invest a lot to deliver on its pipeline?
Yeah. So thank you for asking that question. So I keep talking about the focus. And part of focus is deciding what you're going to do and what you're not going to do. In the beginning of this year, notwithstanding that we have great opportunities, for instance, in gastric, ovarian, we've learned a lot. We think we know how to go back and tackle ovarian, hepatocellular carcinoma. So we have many more solid tumor opportunities. But we've consciously decided to focus on CNS, non-small cell lung, and pancreatic. So those are going to be our focus areas. We have built the G&A to go after those opportunities. R&D is something under our control. And I could do, and most of the R&D is driven by phase three trials.
I could do more phase three trials, but we're going to keep that number about where it is today and keep that number around $200 million until we have the revenue to pay for more. Sales, we've built out the thoracic and the CNS, so I don't expect any more. And for instance, when we launch METIS, that layers right into the existing sales force. So the only place I would see significant growth in the expense space is come the middle of 2026 or when we go to launch pancreatic. And there we'll need another 50 of outside facing. So in large respect, we have built the company we need. And I think you've also seen one of the things we did this year is we restructured our balance sheet. That was always a question, how are you going to deal with your convert?
We will pay that back when it comes due. And we've secured a line of debt. So we are confident that we can execute our plans with the balance sheet as it is now configured. And that should be transparent to everyone.
Should Novocure be a top decile MedTech revenue growth company? I know 2025 is transition, but when you look at 2026 and beyond?
That would be my expectation. We don't guide, but that's why I come to work every morning. If you look at the opportunity, if you look at the approvals, that's why we're all working.
Understood. Fantastic. Well, that we're out of time, Bill.
Okay. Thank you.
Thank you for the time.